Project Summary/Abstract Over 490,000 spinal fusions are performed annually in the US of which 30% undergo revision due to failure to fuse. The mean age for spinal fusion increased from 48.8 to 54.2 years in 2008. In patients older than 50 years, the frequency of osteoporosis is reported to be 50% in women and 15% in man. These patients experience substantial deterioration in the quality of life, increased dependency on others, and reduced lifespan. Vertebral interbody spinal fusion through osteoinductive therapy was developed to prevent or reduce much of this suffering and extend lives. However, the current therapy for this, BMP-2 (Medtronic Infuse?), has been shown to lead to significant inflammation, bone cyst formation, ectopic bone formation, nerve root injury, and cancer. Unlike BMP-2, Osteoactivin (rOA), a recombinant protein, induces bone fusion without inflammation or other complications. Preliminary data shows that it can successfully regenerate bone and it was successful in L4 and L5 spinal fusion in healthy male rats. Recently, a small peptide version of OA (OA-p) was discovered and shown to equivalently regenerate bone. This is exciting because a small peptide provides higher potency and targeting than a small molecule while maintaining a smaller size and decreases toxicity and accumulation potential than the whole protein, and so can be used repeatedly in the same individual. Therefore, in this Phase I SBIR study, we propose to evaluate the commercial feasibility of OA-p for spinal fusion, specifically by testing it in the ovariectomized osteoporotic rat. If successful, this work will demonstrate the potential of OA-p to be used as a novel osteoinductive therapy for accelerating spinal fusion without the complications associated with BMP-2, and with potential extension to other applications.